Methods for treatment of disease using galvanic vestibular stimulation

ABSTRACT

Methods are provided for treating diseases by altering body mass composition in a human subject through application of galvanic vestibular stimulation (GVS) using electrodes placed in electrical contact with the subject&#39;s scalp at a location corresponding to each of the subject&#39;s left and right vestibular systems. The methods may be used to treat obesity-related diseases such as diabetes, hypertension, type 2 diabetes mellitus and osteoporosis. GVS may be applied for a predetermined period of time at regular intervals.

RELATED APPLICATIONS

This application is a continuation of Ser. No. 15/644,727, filed Jul. 7,2017, now U.S. Pat. No. 10,675,465, issued Jun. 9, 2020, which is acontinuation-in-part of U.S. application Ser. No. 14/770,333, filed Aug.25, 2015, now U.S. Pat. No. 9,731,125, issued Aug. 15, 2017, which is aNational Stage Application of PCT International Application No.PCT/US2014/019658, filed Feb. 28, 2014, and which claims priority toU.S. Provisional Application No. 61/771,766, filed Mar. 1, 2013, all ofwhich are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to a device and method for vestibularstimulation to produce physiological changes in an individual's bodymass composition.

BACKGROUND OF THE INVENTION

Obesity is a medical condition which involves the accumulation of excessbody fat. It is defined by body mass index (BMI), which is a measure ofbody weight based upon an individual's weight and height.(BMI=mass(kg)/(height(m))2). Obesity is defined, by both the WorldHealth Organization and the National Institutes of Health, as a BMIgreater than or equal to 30, and pre-obesity is defined as a BMI in the25 to 30 range. Obesity is one of the leading preventable causes ofdeath worldwide, and is thought to reduce life expectancy by around 7years. Excess body fat in itself can also cause significant perceivedissues with cosmesis in healthy individuals.

Many different techniques have been employed to assist individuals whoare overweight to lose weight. These include multiple different types ofdiet, exercise regimes, weight loss medications and weight loss surgery.There is currently no easy or universally effective weight losssolution.

Osteoporosis is a disease of bones that is characterized by a reductionin bone mineral density (BMD), with the result that there is anincreased risk of fracture. The World Health Organization definesosteoporosis as a BMD that is 2.5 standard deviations or more below themean peak bone mass (average of young, healthy adults) as measured bydual energy X-Ray absorptiometry. The development of osteoporosis isdetermined by the interplay of three factors: first, an individual'speak BMD; second the rate of bone resorption; third, the rate offormation of new bone during remodelling. It is a particular healthconcern with aging populations in the developed world, especially inpost-menopausal women. A variety of pharmacological treatments have beenemployed to treat osteoporosis with the mainstay of current managementbeing bisphosphonates, which alter the rate that bone is resorbed.

Centrifugation can in effect mimic a gravitational field greater thanthat experienced on the surface of the Earth (1 G), referred to as“hypergravity” (Smith, 1992). It has been observed that chroniccentrifugation of animals leads to an alteration of body masscomposition (Fuller et al., 2000; Fuller et al., 2002). In particular,animals subjected to hypergravity via centrifugation exhibit a shift in“the proportional distribution of body mass between fat and fat-freecomponents” (Fuller et al., 2000), with a reduction in body fat that isproportional to field strength (Fuller et al., 2002).

Hypergravity has been reported to specifically bring about a reductionin the body fat of chickens (Evans et al., 1969; Smith & Kelly, 1963;Smith & Kelly, 1965; Burton & Smith, 1996), hamsters (Briney & Wunder,1962), other domestic fowl (Smith et al., 1975), rabbits (Katovich &Smith, 1978), mice (Oyama & Platt, 1967; Keil, 1969; Fuller et al.,2000; Fuller et al., 2002) and rats (Oyama & Platt, 1967; Oyama &Zeitman, 1967; Pitts et al., 1972; Roy et al., 1996; Warren et al.,1998). The observed decrease in body fat can be quite significant. Forexample, it has been reported that chickens will decrease from 30% bodyfat at 1 G to 3% at 3 G (Burton & Smith, 1996). Similarly, mice livingat 2 G showed approximately a 55% reduction in absolute and percentagecarcass fat (Fuller et al., 2000). This seems to be accompanied by anincreased usage of fatty acids as a metabolic substrate, and anincreased metabolic rate (Fuller et al., 2006).

While marked loss of fat appears to be the principal change in body masscomposition to hypergravity, and with it an increase in the relativesize of the body's fat-free component, specific changes to the musclesand bones of animals subjected to chronic centrifugation have also beennoted by some authors. Small laboratory animals adapted to a 2 Genvironment have been reported to increase their skeletal mass (asmeasured using body calcium content) by around 18% (Smith, 1992). Jaekelet al. (1977) also reported that prolonged centrifugation at 2.76 G ledto an increased bone mineral density in rat thigh bones.

The balance between flexor and extensor muscles has been observed toshift in response to hypergravity to favor muscles with an anti-gravityfunction (Smith, 1992). In domestic fowl on Earth the legextensor:flexor muscle mass ratio is 0.85 but 2 G altered this ratio to1.17 (Burton & Smith, 1967; Smith, 1992). There also appears to be afunctional difference in the muscles of animals exposed to hypergravity.Animals adapted to 2.5 G have been reported to demonstrate a markedlyincreased exercise capacity (as measured by running to exhaustion), ofabout three-fold that of non-adapted controls, and an increased maximumoxygen uptake (Burton and Smith, 1967, 1996). Hamsters exposed to a 4 Genvironment for 4 weeks were similarly found to have a greaterresistance to fatigue in the gastrocnemius muscle and a 37% increase inthe strength of its tetanic contraction (Canonica, 1966).

Functional adaptations in the muscles of rats adapted to hypergravityhave been examined by analysis of the protein called myosin heavy chain(MHC) (Fuller et al., 2006). Adult rats exposed to 2 G for eight weekswere found to have altered MHC characteristics in their soleus andplantaris muscles (Fuller, 2006). Soleus tends to have more slow-twitchfibers, which are better at endurance activities, and plantaris hasrelatively more fast-twitch fibers, which are better for sprinting buttend to fatigue more rapidly (Gollnick et al., 1974; Fuller et al.,2006). Fuller et al. (2006) found that the rats adapted to 2 G had anincrease in the slow twitch form of MHC (MHC1) in their soleus muscles,and a converse increase in the fast twitch form of MHC (MHC2b) in theirplantaris muscles.

Several mechanisms have been proposed to explain these physiologicalchanges, either alone or in conjunction, including: alterations inmitochondrial uncoupling proteins; fluid volume shifts; alterations inintracranial pressure; increased loading of skeletal muscles; alteredfeeding behavior; and activation of the vestibular system (Fuller etal., 2000; Fuller et al., 2002). The vestibular system, which is a majorcontributor to our sense of balance and spatial orientation, consists ineach inner ear of three semicircular canals (which detect rotationalmovement) and the two otolith organs, termed the utricle and saccule,which detect linear acceleration and gravity (Khan & Chang, 2013). Theyare called otolith organs as they are fluid filled sacs containingnumerous free moving calcium carbonate crystals—called otoliths—whichmove under the influence of gravity or linear acceleration to act uponreceptor cells to alter vestibular afferent nerve activity.

Experiments using mutant mice have suggested that the otolith organs areof particular importance in producing the physiological changes observedin animals subjected to chronic centrifugation. In the first experiment,wildtype mice and a type of mutant mice that lack otolith organs buthave intact semicircular canals were subjected to 8 weeks of chroniccentrifugation at 2 G (Fuller et al., 2002). At the end of this periodthe percentage body fat was significantly reduced in the wildtype miceliving at 2 G compared to a control population living at 1 G (8.5% cf15.5%), and the percentage lean muscle mass was significantly increasedcompared to the control population (91.5% cf 83.1%). However, the mutantmice (lacking otolith organs) living at 2 G showed no significant changein their body mass composition compared to mutant mice living at 1 G.

The second study involved subjecting wildtype and mutant mice (withoutotolith organs) to just two hours of centrifugation at 2 G (Fuller etal., 2004). In the wildtype mice, the authors reported widespreadactivation (as determined by c-fos upregulation) of a variety of brainstructures known to be important in homeostasis and autonomic nervoussystem regulation including: the dorsomedial hypothalamus (a brain areathought to be of major importance in overseeing feeding behavior and infixing a set point for body mass (Fuller et al., 2004)); theparabrachial nucleus; the bed nucleus of the stria terminalis; theamygdala; the dorsal raphe; and the locus ceruleus. These findings werenot observed in the mutant mice.

The vestibular nuclei (which are located in the pons and medulla andreceive input via the vestibular nerve from the vestibular system) arethought to project (both directly and indirectly via the parieto-insularvestibular cortex (PIVC)) to the brainstem homeostatic sites of theparabrachial nucleus (PB) and the peri-aqueductal gray (PAG) (seeChapter 1 and Chapter 3, Section 8 in doctoral thesis by McGeoch, 2010).The PB seems to act to maintain homeostasis—i.e., a stable internalphysiological milieu—by integrating this vestibular input withsympathetic input (via lamina 1 spino- and trigemino-thalamic tractfibers) and parasympathetic input (via the nucleus of the solitarytract) (Balaban and Yates, 2004; Craig, 2007; Craig, 2009; McGeoch etal., 2008, 2009; McGeoch, 2010).

It is thought that the PB then acts to maintain homeostasis by means ofbehavioral, neuroendocrine, and autonomic nervous system efferent (i.e.,both sympathetic and parasympathetic) responses (Balaban and Yates,2004; McGeoch, 2010). Anatomically the PB projects to the insula andanterior cingulate, amygdala and hypothalamus. The insula and anteriorcingulate are areas of cerebral cortex implicated in emotional affectand motivation, and hence behavior (Craig, 2009). The hypothalamus playsa vital role in coordinating the neuroendocrine system and, particularlyvia its dorsomedial aspect, oversees feeding behavior and fixes a setpoint for body mass composition (Balaban and Yates, 2004; Fuller et al.,2004; Craig, 2007). The amygdala (together again with the hypothalamusand insula) is similarly known to be important in autonomic nervoussystem control. The PB also outputs to the PAG and basal forebrain,which are also involved in homeostasis (Balaban and Yates, 2004).

The vestibular system is also known to input to the rostralventro-lateral medulla (RVLM), which is a major sympathetic controlsite, and it seems likely that any observed modulatory effect ofvestibular stimulation on sympathetic function will, at least in part,be mediated via the RVLM (Bent et al., 2006; Grewal et al., 2009; James& Macefield 2010; James et al., 2010; Hammam et al., 2011). However, asthe semicircular canals are not involved in modulating sympatheticoutflow during vestibular stimulation (Ray et al., 1998), anysympathetic modulation arising from vestibular stimulation must beattributable to activation of the otolith organs (i.e., the utricle andsaccule). It is known that white adipose tissue, which constitutes thevast majority of adipose tissue in the human body, is innervated by thesympathetic nervous system and that this innervation regulates the massof the adipose tissue and the number of fat cells within it (Bowers etal., 2004).

The sympathetic nervous system is also known to innervate mature longbones and by this means plays a modulatory role in bone remodelling(Denise et al., 2006). Bilateral vestibular lesions in rats lead to adecrease in the mineral density of weight bearing bones (Denise et al.,2006). However, this reduction is prevented by the adrenoceptorantagonist propranolol (Denise et al., 2006), which suggests a directinteraction between the vestibular inputs and the sympathetic nervoussystem. Hence, it appears that the reported increase in bone mineraldensity in response to hypergravity (Jaekel et al., 1977; Smith, 1992),may also be mediated by a vestibulo-sympathetic effect.

There are also data showing direct pathways connecting the vestibularnuclei with the dorsomedial hypothalamus (Cavdar et al., 2001), which isthe part of the hypothalamus already mentioned as being specificallyinvolved in regulating feeding behavior and setting a fixed point forbody mass (Fuller et al., 2004).

The hormone leptin is secreted by fat cells and acts upon thehypothalamus to regulate food intake and energy expenditure. Leptin actsto suppress food intake and increase energy expenditure (Hwa et al.,1997), and as such plays a role in regulating body weight. Notably,vestibular stimulation has been found to cause an increase in leptinrelease (Sobhani, 2002; Sailesh & Mukkadan, 2014).

A chemical approach to vestibular stimulation may be based onbetahistine, a partial histamine-3 (H3) receptor antagonist that hasbeen used for some time to treat Meniere's disease. It is also knownthat by blocking presynaptic H3 receptors, betahistine causes anincreased release of histamine and activation of H1 receptors, which isthe opposite action to antihistaminic vestibular suppressants (Barak etal., 2008; Baloh & Kerber, 2011). Some early reports have suggestedthat, at least in certain subgroups, betahistine may be an effectiveweight loss medication (Barak et al., 2008). Conversely vestibularsuppressant medications often lead to weight gain.

Various techniques have been used for research and clinical purposes tostimulate some or all of the components of the vestibular system inhumans (Carter and Ray, 2007). These include: (1) Caloric vestibularstimulation, which involves irrigating the outer canal of the ear withwarm or cold water or air and mainly stimulates the lateral semicircularcanal of that ear; (2) Yaw head rotations, which activates both lateralsemicircular canals; (3) Head-down rotation to activate otolith organsand also, initially, semicircular canals; (4) Linear acceleration, whichactivates otolith organs; (5) Off-vertical axis rotation (OVAR), whichactivates otolith organs; (6) Galvanic vestibular stimulation (“GVS”),which activates all five components of the vestibular apparatussimultaneously using an electrical current (Fitzpatrick & Day, 2004; St.George & Fitzpatrick, 2011); (7) Click induced vestibular stimulationusing an auditory click (Watson & Colebatch, 1998); and (8) Neck musclevibration induced vestibular stimulation (Karnath et al., 2002). Ofthese techniques, only one offers the practical option of being producedcommercially for home use without expert supervision—GVS.

GVS involves stimulating the vestibular system through thetranscutaneous application of a small electric current (usually between0.1 to 3 milliamps (mA)) via two electrodes. The electrodes can beapplied to a variety of locations around the head, but typically one isapplied to the skin over each mastoid process, i.e., behind each ear.Some authors term this a “binaural application.” If a cathode and ananode are used with one placed over each mastoid, which is the mostcommon iteration, then this is termed a bipolar binaural application ofGVS. The current can be delivered in a variety of ways, including aconstant state, in square waves, a sinusoidal (alternating current)pattern and as a pulse train (Petersen et al., 1994; Carter & Ray, 2007;Fitzpatrick & Day, 2004; St. George & Fitzpatrick, 2011).

An electronic appetite suppressant device known as the FOOD WATCHER™ wasavailable on the market in the United Kingdom until recently. Thepremise behind the FOOD WATCHER™ was that it would act to electricallyactivate acupuncture points on the ears, with the consequence that auser's appetite would be suppressed. Additionally it was argued that itmay suppress appetite by activating the vagus nerve (Esposito et al.,2012).

The FOOD WATCHER™ electrodes were conically shaped plugs designed to beinserted into the external auditory canals (Esposito et al., 2012). TheFOOD WATCHER™ is reported to have generated a “signal with amplitude of40V, frequency of 50 Hz and current of 40 mA through the ear plugs”(Esposito et al., 2012).

A study was carried out on 40 overweight and obese healthy volunteers toinvestigate the effectiveness of the FOOD WATCHER′ (Esposito et al.,2012). Ten volunteers received the FOOD WATCHER™ and a hypocaloric diet,ten received a hypocaloric diet alone, ten received the FOOD WATCHER™and a high-protein diet, and ten a high protein diet alone. The authorsfound that “after 2 months of simultaneous treatment with electricstimulation and diet there was an average weight loss of 7.07 kg in thehypocaloric group and 9.48 kg in the high-protein group, whereas anaverage weight loss of 5.9 kg and 7.17 kg were observed with hypocaloricand high-protein diet alone, respectively”, leading the authors toconclude that electrical stimulation through the ears may help withweight loss, particularly when used with a high-protein diet, possiblyacting via a Yin-yang acupuncture energy balance.

Muscle sympathetic nerve activity (MSNA) to the blood vessels inskeletal muscle can be measured directly in man using microelectrodes.It has been reported that GVS delivered as square wave pulses (at 2 mAof 1 second duration) was ineffective at altering MSNA (Bolton et al.,2004; Carter & Ray, 2007). Conversely, delivering GVS (with an electrodeover each mastoid) more dynamically is effective at modulating MSNA.This has been shown using both pulse trains (specifically 10, 1 mspulses across 30 ms and time-locked to the R wave of theelectrocardiogram) (Voustianiouk et al., 2005), and sinusoidal GVS (−2to 2 mA, 60-100 cycles, applied at administered bipolar binaural GVS (±2mA, 200 cycles) at frequencies of 0.2, 0.5, 0.8, 1.1, 1.4, 1.7 & 2.0 Hz,to 11 human volunteers while measuring their MSNA (Grewal et al., 2009).

Grewal et al. found a degree of cyclic modulation of MSNA at allfrequencies, however, vestibular modulation of MSNA was significantlystronger at 0.2 Hz and significantly weaker at 0.8 Hz. This suggested“that low-frequency changes in vestibular input, such as thoseassociated with postural changes, preferentially modulate MSNA.”Conversely, it was proposed that vestibular inputs around the frequencyof the heart rate (i.e., 0.8 Hz, which is 48 beats per minute) competewith, and are inhibited by, the modulation of the MSNA by baroreceptors(pressure detecting mechanoreceptors in the walls of blood vessels),which are activated at the frequency of the heart rate.

The baroreceptor reflex is believed to act via the parasympatheticnervous system (including the vagus nerve and nucleus of the solitarytract) to inhibit the action of the RVLM. This inhibition may bemediated, at least in part, via the caudal ventrolateral medulla (Svedet al., 2000).

Additional evidence to support the argument that vestibular inputs witha frequency distinct from the cardiac frequency are more potent atmodulating MSNA, is found in a study in which 8 human subjects weregiven sinusoidal GVS at their own cardiac frequency, and at ±0.1, ±0.2,±0.3, ±0.6 Hz from this frequency (James & Macefield, 2010). The authorsreport that the modulatory effect of the GVS on MSNA activity wasimpaired when its frequency was closer to the cardiac frequency.

The same authors also measured skin sympathetic nerve activity (SSNA),using microelectrodes, in 11 volunteers subjected to bipolar binauralGVS over the mastoid processes (±2 mA, 200 cycles) at 0.2, 0.5, 0.8,1.1, 1.4, 1.7 and 2.0 Hz (James et al., 2010). Marked entrainment of GVSwas found at all frequencies, although it was significantly weaker at2.0 Hz. In contrast to the pattern observed with vestibular modulationof MSNA (Grewal et al., 2009), it was reported that the pulse relatedmodulation of SSNA was greater at 0.8 Hz than at 0.2 Hz.

In a recent study, this group found that low frequency sinusoidal GVS(at 0.08, 0.13 and 0.18 Hz) caused two peaks of MSNA modulation (Hammamet al., 2011). This suggested that the primary peak occurs from thepositive peak of the sinusoid in which the right vestibular nerve ishyperpolarized and the left depolarized, with the secondary peak of MSNAmodulation occurring during the reverse scenario. This behavior was notobserved at higher frequencies, possibly because there was insufficienttime for a secondary peak to be produced. The authors suggest that thisfinding indicates “convergence of bilateral inputs from vestibularnuclei onto the output nuclei from which MSNA originates, the rostralventro-lateral medulla.”

Various uses for vestibular stimulation have been described in relatedart, including: treating motion sickness (U.S. Pat. No. 4,558,703 toMark); headsets for stimulation in a virtual environmental (U.S. Pat.No. 6,077,237 to Campbell, et al.); counteracting postural sway (U.S.Pat. No. 6,219,578 to Collins, et al.); to induce sleep, controlrespiratory function, open a patient's airway and/or counteract vertigo(U.S. Pat. No. 6,748,275 to Lattner, et al.); an in-ear caloricvestibular stimulation apparatus (U.S. Pat. No. 8,262,717 to Rogers, etal.); and to alleviate anxiety (U.S. Pat. No. 8,041,429 to Kirby).

Patent applications have been filed for the following: a method ofdelivering caloric vestibular stimulation (US Patent Publication2011/0313498 to Rogers, et al.) and a system and method for reducingsnoring and/or sleep apnea in a sleeping person, which may involve theuse of GVS (US Patent Publication 2008/0308112 to Bensoussan). Chan, etal. have filed several patent applications for a variety of uses of GVSincluding: an adaptive system and method for altering the motion of aperson (US Patent Publication 2010/0114256); a system for alteringmotional responses to sensory input (US Patent Publication2010/0114255); a system and method for providing therapy by altering themotion of a person (US Patent Publication 2010/0114188); a system andmethod for providing feedback control in a vestibular stimulation system(US Patent Publication 2010/0114187); a system for altering the motionalresponse to music (US Patent Publication 2010/011418); a system andmethod for game playing using vestibular stimulation (US PatentPublication 2010/0113150); a system and method of altering the motionsof a user to meet an objective (US Patent Publication 2010/0112535); anda system and method of training to perform specified motions byproviding motional feedback (US Patent Publication 2010/0112533).

GVS is also known to stimulate all components of the vestibularapparatus, including the two otolith organs, and dynamic forms of GVS(i.e., pulse train and sinusoidal) appear to be effective at modulatingsympathetic activity. If bipolar binaural sinusoidal GVS is used, themodulation of MSNA is greater when it is administered at a frequencydistinct from the cardiac frequency.

In spite of the many reported uses of GVS in the prior art, there hasbeen no teaching or suggestion to apply GVS to alteration of body masscomposition in humans. The present invention is directed to such anapplication.

SUMMARY OF THE INVENTION

According to the present invention, methods are provided for treatmentof disease using galvanic vestibular stimulation to alter body masscomposition in humans. In an exemplary embodiment, sinusoidal or pulsetrains of galvanic current are applied via electrodes applied to asubject's scalp to stimulate the otolith organs and activate thevestibular system. The alteration of body mass composition may includeone or more of the following effects: a decrease in body fat; a relativeincrease in lean muscle mass; and an increase in bone mineral density.The present invention may be used to treat diseases including obesity,diseases associated with obesity (e.g., type 2 diabetes mellitus andhypertension), osteoporosis, or it may be used as an aid in physicaltraining to improve relative lean muscle mass and improve the exercisecapacity of that muscle.

In an exemplary embodiment, vestibular stimulation, preferably via GVS(likely administered in a sinusoidal or pulse-train manner), is appliedto modulate body mass composition in order to bring about: a decrease intotal body fat; an increase in lean muscle mass; and an increase in bonemineral density. This effect will likely take place via activation ofthe otolith organs of the inner ear by GVS and subsequent modulation ofsympathetic nervous system activity, which is likely to be mediated viathe RVLM. Additionally, this effect may also involve brain structuressuch as brainstem homeostatic sites (specifically the PB, PAG), thePIVC, amygdala, insula and the hypothalamus. The effect may also bemediated via an effect on the release of certain hormones, such asleptin. The efficacy of the invention is likely to be greater if bipolarbinaural GVS (with an electrode over each mastoid process) isadministered in a dynamic manner (e.g. sinusoidal or pulse train).

In one aspect of the invention, a method for treating disease in a humansubject comprises treating the disease by applying galvanic vestibularstimulation (GVS) to the subject.

In another aspect of the invention, a device for altering body masscomposition in a human subject includes electrodes disposed inelectrical contact with the subject's scalp at a location correspondingto each of the subject's left and right vestibular system; and a currentsource in electrical communication with the electrodes for applyinggalvanic vestibular stimulation (GVS) to the subject. In one embodiment,the current source produces a constant current within a predeterminedvoltage range. The current source may produce a current havingalternating polarity. The current source may further include a feedbackloop for measuring a resistance across the subject's scalp and adjustinga voltage output to maintain a constant current across the subject'sscalp. The current produced by current source may be within a range of0.001 mA to 5 mA. The current produced by the current source may besinusoidal with a frequency that is less than the subject's cardiacfrequency.

In a further aspect of the invention, a method for altering body masscomposition in a human subject comprises applying galvanic vestibularstimulation (GVS) to the subject. The GVS can be applied by disposing anelectrode on the subject's scalp proximate to each mastoid process. TheGVS may be a current having a constant level and an alternatingpolarity. In one embodiment, the constant current level can bemaintained by a feedback loop adapted to measure a resistance across thesubject's scalp and adjust a voltage output to maintain the currentlevel. The GVS may be a sinusoidal current having a frequency that isless than the subject's cardiac frequency. The GVS may be applied for apredetermined period of time at a regular interval, which may be daily,weekly, or a combination thereof.

In yet another aspect of the invention, a method of decreasing totalbody fat in a human subject in need thereof comprises applying galvanicvestibular stimulation (GVS) to the subject. Still another aspect of theinvention is a method of increasing relative percentage lean muscle massin a human subject in need thereof by applying galvanic vestibularstimulation (GVS) to the subject. In a further aspect of the invention,a method of increasing bone mineral density in a human subject in needthereof includes applying galvanic vestibular stimulation (GVS) to thesubject.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be better understood from the followingdetailed description of some preferred embodiments of the invention,taken in conjunction with the accompanying drawings, in which likenumbers correspond to like parts, and in which:

FIG. 1 is a schematic diagram of an exemplary stimulator circuit.

FIG. 2 is a schematic diagram of an alternative embodiment of thestimulator circuit with a gain control component.

FIG. 3 is a schematic diagram of a second alternative embodiment of thestimulator device.

FIGS. 4A and 4B illustrate exemplary wave forms generated by the device.

FIG. 5 is a diagram showing an exemplary GVS electrode placement.

FIG. 6 is a diagram illustrating the vestibular system of the left innerear.

FIG. 7 is a sample report showing the results of a first DXA scan of ahuman subject.

FIG. 8 is a sample report showing the results of a second DXA scan ofthe same human subject following a series of GVS stimulations.

FIG. 9 is a diagram illustrating an exemplary wave form for use indelivering GVS.

FIG. 10 is a graph illustrating indirect calorimetry measurements fromtreatment using the exemplary waveform illustrated in FIG. 9.

DETAILED DESCRIPTION

FIGS. 1 and 2 illustrate one possible embodiment of the GVS circuitrythat can be employed to carry out the method of the present invention.The device 20 includes a source of time-varying galvanic current thatmay be software programmable using a microcontroller.

FIG. 1 illustrates the basic components of an embodiment of thestimulation device 20, which includes an operational-amplifier(“op-amp”) based constant-current source. A voltage is placed across thescalp 10 through electrodes 4 and 6 and measured by the op-amp 12. Inthe exemplary embodiment, op-amp 12 may be a general purpose operationalamplifier, an example of which is the LM741 series op-amp, which iswidely commercially available. Selection of an appropriate operationalamplifier will be within the level of skill in the art. If the voltagereturning from the scalp 10 to pin 2 (inverting input) of op-amp 12 isdifferent than the reference voltage +9V at pin 3 (non-inverting input),the operational amplifier draws from the +18V input through pin 7 toincrease the amount of voltage output at pin 6, thereby increasing thecurrent across the scalp 10 to maintain a constant current level. Loadresistor 16 is 250 ohms. Adjustment of potentiometer 14 provides gaincontrol by decreasing the voltage input into op-amp 12 at pin 2, thuscontrolling the amount of current flowing across the scalp. In thepreferred embodiment, the +9V and +18V inputs are provided by one ormore batteries (not shown), or a conventional DC converter may be usedwith appropriate safety provisions.

The schematic in FIG. 2 adds control components to the basic stimulatorcircuit 20 of FIG. 1. Transistor 22, powered by thepulse-width-modulation (PWM) output (MOSI (master output/slave input,pin 5) of an ATtinyl3 microcontroller 24 (Atmel Corporation, San Jose,Calif.) or similar device, may be used to control the gain of thestimulator. The PWM causes the transistor to draw more or less of thevoltage entering the Op-Amp 12 (pin 2) to ground, thus modulating theamount of current flowing across the scalp.

In a preferred embodiment, the device components and any externalinterfaces will be enclosed within a housing 30 (shown in FIG. 5) withappropriate user controls 32 for selecting stimulation parameters asappropriate. Note that a knob is shown for illustrative purposes onlyand that other types of controls, including switches, buttons, pressurebumps, slides, touch screens or other interface devices may be used.Optional design components that may be added to expand the functionalityof the device include a memory storage device, such as a memory card orelectrically erasable programmable read-only memory (EEPROM), which willallow the time, duration, and intensity of stimulations to be recorded.This can be accomplished by programming the microcontroller 24 to outputa logic-level 3.4V pulse (TTL (transistor-transistor logic)) from theremaining digital out (MISO (master input/slave output, pin 6) to asecure digital (SD) memory card, EEPROM, USB flash drive or other datastorage device via an appropriate port on the device housing.Additionally, the +18V input may be derived by integrating a chargepump, or DC-DC step-up converter, such as the MAX629 or MAX1683 (notshown). This design feature would have the benefit of reducing the sizeof the device by producing the necessary +18V input from smallerbatteries, which can be disposable or lithium ion rechargeable.Additional features may include wireless communication circuitry, as isknown in the art, for programming and/or data collection from a remotecomputing device, which may include a personal computer, smart phone ortablet computer.

Other functions for implementing GVS in the present invention mayinclude the ability to pulse the current at precise intervals anddurations, in a sinusoidal wave with adjustable amplitude and period,and even switch polarity at precise intervals.

Additional options for facilitating and/or enhancing the administrationof GVS may include a built-in biofeedback capability to adjust thestimulation parameters for optimal effect based on signals generated bysensors that monitor the subject's activity and/or biometriccharacteristics, such as motion, position, heart rate, etc. For example,real-time heart measured by a heart-rate sensor or monitor can be usedas input into the GVS device, triggering an automatic adjustment of thesinusoidal GVS frequency to an appropriate, possibly pre-programmed,fraction of the cardiac frequency. Real-time data on the user's motionor position measured by accelerometers may also be used as input tocontrol stimulation, to improve effectiveness and safety. For example,treatment could be terminated if excessive motion or change in theuser's position is detected, or the user can be alerted about changes inposition that could have adverse effects. The heart rate sensor/monitorand/or accelerometers may be separate devices that communicate with theinventive GVS device through a wired or wireless connection.Alternatively, sensors may be incorporated directly into the GVS deviceto form a wearable “sense-and-treat” system. As new sensors aredeveloped and adapted to mobile computing technologies for “smart”,wearable mobile health devices, a “sense-and-treat” GVS device mayprovide closely tailored stimulation based on a wide array of sensordata input into the device.

FIG. 3 schematically illustrates an exemplary prototype of the inventivedevice 40 implemented using the widely commercially-available ARDUINO®Uno single board microcontroller 42 (Arduino, LLC, Cambridge, Mass.),which is based on the ATmega328 microcontroller (ATMEL® Corporation, SanJose, Calif.). Microcontroller 42 includes fourteen digital input/outputpins (of which six can be used as pulse width modulation (PWM) outputs),six analog inputs, a 16 MHz ceramic resonator, a USB connection, a powerjack, an ICSP header, and a reset button. The +14.8 V DC power to thecircuit is provided by batteries 49. For example, four lithium ionbatteries, each providing 3.7V (1300 mAh) are used, and are preferablyrechargeable via charging port 51.

The PWM allows the output waveform to be accurately controlled. In thiscase, the waveform takes a repeating half-sine wave pattern in apositive deflection, as shown in FIG. 4A. The frequency has beenpredefined as 0.5 Hz, but may be set to a different value by manualcontrol or in response to input from a sensor, such as a heart ratesensor (see, e.g., FIG. 5). The user can manually control the amplitudeby adjusting the potentiometer 48, allowing a range of 0 to 14.8V to besupplied to the electrodes. This adjustment may be effected by rotatinga knob, moving a slide (physically or via a touch screen), or any otherknown user control mechanism. Alternatively, the potentiometer settingcan automatically adjust in response to an input signal from a sensor.Relay 44 communicates the voltage adjustment to a graphical display 45to provide a read-out of the selected voltage and/or current.

A relay 46 may be employed to effectively reverse the polarity of thecurrent with every second pulse. The effect of this is shown in FIG. 4B,where the sinusoidal pattern changes polarity, thus generating acomplete sine waveform to produce alternating periods of stimulation, onthe order of 1 second in duration, to the left and right mastoidelectrodes 50L and 50R.

The device may optionally include a three color LED 52 that provides avisual display of device conditions, i.e., diagnostic guidance, such asan indication that the device is working correctly or that the batteryrequires recharging.

Optional design components may include a touch screen configuration thatincorporates the potentiometer controls, a digital display of voltageand current, plus other operational parameters and/or usage history. Forexample, remaining battery charge, previous stimulation statistics andvariations in resistance could be displayed. Additional features mayinclude controls for alterations in the waveform such as change offrequency and change of wave type (for example square, pulse or randomnoise). The ARDUINO® microprocessor platform (or any similar platform)is ideally suited to incorporate feedback control or manual control offrequency, intensity or other stimulation parameters based on anexternal signal source. For example, the ARDUINO® microprocessorplatform, if provided with BLUETOOTH® capability, can be wirelesslycontrolled by an iPHONE®, ANDROID®, or other smart phone, laptop orpersonal computer, tablet or mobile device, so that the touchscreen ofthe mobile device can be used to control and/or display the GVSstimulation parameters rather than requiring a dedicated screen on thedevice. The mobile device may also be configured to store and analyzedata from previous stimulations, providing trends and statistics aboutlong periods of stimulation, such as over 6 months. Applications of thiscould allow for programs to monitor and guide users on their progressand goals, highlighting body measurements and changes in weight relativeto the periods of stimulation.

An exemplary operational sequence for the embodiment of FIG. 3 for usein effecting an alteration in body mass composition may include thefollowing steps:

-   -   1. When the push button power switch 41 is activated, the        battery(ies) 49 supply 5 volts DC to the microprocessor 42        through a 5 volt regulator and a 1 amp fuse (shown in the figure        but not separately labeled.)    -   2. The LED 52 will flash green three times to indicate the power        is “on”. If the blue light flashes the battery needs charging.        While the voltage is supplied to the electrodes 50L and 50R, the        LED 52 will flash red at regular intervals, e.g., 30 seconds to        a minute.    -   3. The microprocessor 42 generates a 0.75 VDC half wave sign        wave. The voltage is amplified to 14.8 volts by the amplifier.        The sine wave completes one-half cycle in 1 second (i.e., the        frequency of the sine wave is 0.5 Hz). The voltage can be varied        by the potentiometer 48 from 0 to 14.8 volts.    -   4. After a half cycle is completed, relay 46 switches polarity        of the electrodes 50L, 50R and the microprocessor 42 sends        another half cycle. The relay 46 again switches polarity and        continues for as long as the unit is “on”. This sends a full        sine wave of up to ±14.8 VDC to the electrodes, with the full        voltage swing modulated by the potentiometer 48.    -   5. A digital display 45 provides a visual indication of the        voltage and current delivered to the electrodes 50L, 50R.        Depending on the size and complexity of the display, voltage and        current values may be displayed simultaneously or alternately        for a short duration, e.g., 3 seconds.

Other device options may include user controls to allow the current tobe pulsed at precise intervals and durations, a sinusoidal wave to begenerated with adjustable amplitude and period, and/or to switchpolarity at precise intervals. External control and monitoring via asmart phone or other mobile device as described above may also beincluded. Further input and processing capability for interfacing andfeedback control through external or internal sensors may be included.

FIG. 5 illustrates an exemplary GVS electrode 34 positioned on the skinbehind the pinna of the left ear 36, and over the left mastoid process,of a subject to be treated. The mastoid process is represented by dashedline 38. The right electrode (not shown) would be placed in the samemanner on the skin over the right mastoid process and behind the rightpinna. It should be noted that the illustrated placement of theelectrodes is provided as an example only. In fact, laterality of theelectrode application, e.g., electrodes precisely over both mastoidprocesses, is not believed to be critical, as long as each electrode isin sufficient proximity to the vestibular system to apply the desiredstimulation. The electrodes 34 are connected to stimulation device 40(inside housing 30) by leads 33. Manual control means, illustrated hereas a simple knob 32, may be operated to control the current or otherparameters. As described above, alternative control means include aslide, touch screen, buttons or other conventional control devices.External control signals, for example, a signal from a heart ratemonitor 35, may be input into the device either wirelessly, asillustrated, or by leads running between the sensor and the device.Electrodes such as the widely commercially available 2×2 inch platinumelectrodes used for transcutaneous electrical nerve stimulation (TENS)may be used in order to minimize any possible skin irritation. Aconducting gel 37 may be applied between the subject's scalp and thecontact surface of the electrodes to enhance conduction and reduce therisk of skin irritation.

The amount of current the subject actually receives depends on the scalpresistance (I_(scalp)=V_(electrodes)/R_(scalp)), which may vary as theuser perspires, if the electrode position changes, or if contact withthe skin is partially lost. It appears that the current levels quoted inthe literature could only be delivered if the scalp resistance was muchlower than it actually is. Measurements conducted in conjunction withthe development of the inventive method and device indicate that thetrans-mastoid resistance is typically between 200 to 500 k-Ohm. Thus, ifa GVS device were actually being used to deliver 1 mA, the voltage wouldbe between 200 to 500V according to Ohm's law. The battery-powereddevices that are usually used to administer GVS are simply not capableof generating such an output. Hence, the existing reports appear to beinaccurate with regard to the actual current being delivered in GVS.

Prior art designs lack consideration for each subject's unique scalpresistance, and therefore may not deliver an effective current to eachpatient. In the present invention, this limitation can be overcome bytaking into account inter-subject scalp resistance variability as wellas compensating for fluctuations in the scalp resistance that may occurthroughout the procedure. To compensate for slight and fluctuatingchanges in scalp resistance during the administration of current, theinventive GVS device may include an internal feedback loop thatcontinuously compares the desired current against the actual measuredcurrent across the scalp and automatically compensates for anydifferences. If R_(scalp) increases, the V_(electrodes) increases tocompensate. Conversely, voltage decreases when R_(scalp) drops. Thisdynamic feedback compensation loop provides constant current across thescalp for the duration of the procedure regardless of fluctuatingchanges in electrode-scalp impedance.

FIG. 6 illustrates the vestibular system of the left inner ear. Thecochlea 68, which is the peripheral organ of hearing, is also shown. Itdemonstrates: the anterior 62, posterior 67, and horizontal 63semicircular canals, which transduce rotational movements; and theotolith organs (the utricle 66 and saccule 65), which transduce linearacceleration and gravity. Without intending to be bound by any theory,it is believed that the otolith organs mediate any change in body masscomposition that GVS evokes. The vestibulocochlear nerve 64 (also knownas the eighth cranial nerve) is composed of the cochlear nerve (whichcarries signals from the cochlea), and the vestibular nerve (whichcarries signals from the vestibular system).

Validation

Performance of the present invention was evaluated using dual energyx-ray absorptiometry (DXA), a technique that was originally developed todetermine bone mineral density (BMD) and to aid in the management ofosteoporosis. More recently, the technique has been expanded to includethe analysis of fat mass and lean body mass in addition to BMD. The DXAmachine emits alternating high and low energy x-rays that produceprecise, high quality images. The use of a fan beam allows decreasedscan times so that scans can be completed within seconds or minutes.

The basic principle of DXA data acquisition is based on the differencesbetween bone and soft tissue attenuation at the high and low x-raylevels. As the x-ray beam passes through the subject, detectors registerthe varying levels of x-rays that are absorbed by the anatomicalstructures of the subject. The raw scan data, which includes values oftissue and bone, are captured and sent to a computer. An algorithminterprets each pixel, and creates an image and quantitative measurementof the bone and body tissues.

Whole body DXA scans using a HOLOGIC® Discovery W™ DXA scanner wereconducted to determine bone mineral density, lean mass and whole bodyfat. The technique has a precision error (1SD) of 3% for whole body fatand 1.5% for lean mass. The in vivo precision for the measurement ofbone density using the DXA technique is 0.5-1.5% at the lumbar spine andthe standard deviation of the lumbar spine bone density is 0.01 g/cm².The radiation risk associated with the proposed protocol used is smalland in cumulative total is equal to 0.26 mSv for each subject. Thisamount of radiation exposure is low, typically less than what one wouldreceive from one year of natural exposure, i.e., around 1.6 mSv.

A comparable commercially available GVS device sold under the trademarkVESTIBULATOR™ (Good Vibrations Engineering Ltd. of Ontario, Canada) haspreviously been used in a number of research studies at otherinstitutions. (Barnett-Cowan & Harris, 2009; Trainor et al., 2009.) Thisdevice functions with 8 AA batteries, so that the voltage can neverexceed 12 V. According to the manufacturer's specifications, the maximumcurrent that this device can deliver is 2.5 mA. The present inventionuses a more user-friendly device (e.g., the delivered current can beadjusted using a controller (knob, slide, or similar) on the side of thehousing, in comparison to the VESTIBULATOR™, where a similar adjustmentcan only be carried out by first writing a MATLAB® script and thenuploading it remotely, via BLUETOOTH®, in order to reprogram theVESTIBULATOR's™ settings.) Due to the very small currents used duringGVS, the technique is believed to be safe (Fitzpatrick & Day, 2004;Hanson, 2009). In particular, although electrical current can lead tocardiac arrhythmias, including ventricular fibrillation, the thresholdfor such an occurrence is in the 75 to 400 mA range, well above thecurrent levels the battery powered GVS devices can deliver. Furthermore,the electrodes will only be applied to the scalp, such as shown in FIG.5, and nowhere near the skin over the chest.

Resistive heating can occur with high voltage electrical stimulation ofthe skin. However, the voltage and current (usually below 1 mA)delivered during GVS are well below the levels that pose this risk.Nonetheless, skin irritation can occur due to changes in pH. This may bemitigated by using large surface area (approximately 2 inch diameter)platinum electrodes and aloe vera conducting gels.

It may be desirable to monitor the subject's heart rate (HR) todetermine the cardiac frequency during GVS treatment. The cardiacfrequency can then be used to alter the frequency of the sinusoidal GVSso as to maintain a certain ratio between the cardiac frequency and thefrequency of the sinusoidal GVS to avoid interference with baroreceptoractivity. For example, a sinusoidal GVS frequency to cardiac frequencyratio of 0.5 would be appropriate.

During administration of GVS, one platinum electrode is attached to theskin over one mastoid and the other electrode attached to the skin overthe other, as shown in FIG. 5. The electrodes may be coated withconducting gel containing aloe vera. The device is activated to delivera current of approximately 0.1 mA (given a trans-mastoid resistance ofabout 500 kOhm) with a sinusoidal waveform at 0.5 Hz. A typical currentrange for the device would be around 0.001 mA to 5 mA. The subjectshould remain seated or lying flat throughout the session to avoidmishap due to altered balance during vestibular stimulation. The deviceis set up to automatically stop after one hour however, the subject maydiscontinue the treatment sooner if desired. The subject should remainseated until their balance has returned to normal, which should occurwithin a short period of time after the GVS device has been turned off.

Example 1—23-Year-Old Female Subject

Data accrued for one human subject support the use of GVS as aneffective approach for altering body mass composition to reduce totalbody fat and increase lean muscle mass. The subject was a Hispanicfemale born in 1989 and at the time of the study was 23 years old. Acumulative total of 20 hours of GVS was administered between 8 Oct. 2012and 7 Dec. 2012. Over this two-month period, the subject received onehour of GVS on each stimulation day. No GVS session exceeded one hour onany stimulation day.

At the start and completion of the study (after providing a negativepregnancy test), the subject underwent DXA scans as described above. Thefirst DXA scan was carried out on the day of the first GVS session(before the session) and the second scan was carried out five days afterthe final GVS session. In order to ensure a constant hydration status,the subject was instructed not to exercise within 12 hours of the DXAscans and to refrain from consumption of alcohol, nicotine, andcaffeinated beverages. The subject reported that she was at the samestage of her menstrual cycle at the time of each scan. The subject wasblinded as to whether she was receiving an experimental or placeboprocedure.

The GVS was administered using the bipolar binaural method with anelectrode placed on the skin over each mastoid process (see FIG. 5). Alinear stimulus isolator from World Precision Instruments (A395D) wasused to administer the stimulus, and a 0.5 Hz sinusoidal waveform wasimposed on this stimulus by a signal generator from BK Precision (Model4010A). The subject was seated with her eyes open throughout theadministration. The subject's approximate trans-mastoid resistance(after preparing the skin with micro-abrasive gel) was approximately 500kOhm. To achieve the desired level of stimulation, the current deliveredthroughout each of the GVS sessions was approximately 0.1 mA. Thesubject reported being aware of a swaying sensation during eachstimulation session. The subject made no changes to her dietary habitsand did not engage in exercise during the study period. She was on noregular medications.

The report for the initial baseline DXA scan is provided in FIG. 7.Prior to treatment, testing indicated that the subject had a total bodyfat of 32947.4 g; a total combined bone mineral content (BMC) and leanmuscle mass of 49799.3 g; and a percentage body fat of 39.8%. The secondDXA scan performed after conclusion of the treatment period produced theresults shown in FIG. 8. The post-treatment results indicated total bodyfat of 31839.9 g; a total combined BMC and lean muscle mass of 51890.4g; and a percentage body fat of 38.0%. (The BMC is directly proportionalto the BMD, which as described above is used in the diagnosis ofosteoporosis).

Between the two scans, the subject's combined BMC and lean muscle massincreased by 2091.1 g and total body fat decreased by 1107.5 g. Comparedto the baseline scan, this represents an increase in combined BMC andlean muscle mass of 4.2% and a decrease in total body fat of 3.4%. Thesubject's ratio of total fat to combined BMC and total lean muscle massimproved from 0.66 to 0.61. The data from this subject are thussupportive of the method of using GVS to alter body mass composition asdescribed.

The inventive system and method are based on a novel use of vestibularstimulation, in particular, galvanic vestibular stimulation, to producephysiological changes in an individual human's body mass composition.The application of GVS as described herein simulates some of the effectsof hypergravity, providing a safe, simple, drug-free approach to reducebody fat, increase lean muscle mass and increase bone density. Thesimplicity of the device and its operation makes it possible for anyindividual wishing to modify his or her body mass composition,regardless of whether for health, aesthetic, or athletic performancereasons, to administer stimulation in the privacy of their home. Thedevice may also be used in a medical facility such as a doctor's office,clinic, or physical therapy facility to treat obesity and associateddiseases, treat or prevent osteoporosis, and assist in physical trainingor recovery from injury.

Further Validation

Performance of the present invention was further evaluated using atechnique called indirect calorimetry, which involves wearing a tightlyfitted facemask that measures oxygen consumption and carbon dioxideproduction in order to provide minute-by-minute data on energymetabolism and specifically the type of substrate used in energymetabolism—i.e. the relative proportion that is derived from fat asopposed to carbohydrate (Lam & Ravussin, 2017).

This was carried out on three subjects (a male and two females) whounderwent indirect calorimetry before, during and after a session ofGVS. The subjects started their recording sessions at about 7.30 am,having been fasting, with nothing but water, for the previous 12 hours.All had also refrained from exercise during the preceding 24 hours, andthroughout the recording sessions the subjects sat quietly watchingdocumentaries on a computer tablet.

On this occasion a GVS device, provided by the company Neurovalens Ltd,was used to deliver the stimulation. This device delivers a GVS currentwaveform as illustrated in FIG. 9, which consists of an AC square waveat 0.5 Hz with a 50% duty cycle. The protocol followed was that for thefirst 30 minutes each subject underwent indirect calorimetry alone inorder to establish a baseline. Each subject then underwent a one-hoursession of binaural, bipolar GVS with electrodes placed on the skin overeach mastoid as shown in FIG. 5. As stated above an AC square wave at0.5 Hz with a 50% duty cycle was delivered, in all subjects with acurrent of 0.6 mA, although the device used is capable of deliveringmore.

Indirect calorimetry measurements were ongoing throughout thisstimulation period, and for 30 minutes post-stimulation. The averageddata for these periods is displayed graphically in FIG. 10. Thesedemonstrate that GVS, delivered in the waveform shown in FIG. 9,triggered an increase in the utilization of fat as a metabolicsubstrate, approximately from 56% to 62%. Moreover, this increase in fatmetabolism appears to be sustained beyond the one-hour stimulationperiod, with the data revealing that the increase in fat metabolismcontinued—at more than 11% above baseline—for at least 30 minutes aftercessation of the active vestibular stimulation. It should be noted thatthe pattern adumbrated here from the average, was also seen in eachsubject individually.

The consequence of increasing fat utilization as a metabolic substrate,if done repeatedly over time, would be a reduction in body fat. Also, ofparticular note is that the increase in fat metabolism that occurred inresponse to GVS continued beyond the actual period of stimulation, andif anything accentuated rather than attenuated during the period ofobservation. These findings offer further evidence to support theinventive system and method, that vestibular stimulation, in particularGVS, can produce physiological changes in an individual human's bodymass composition.

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1. A method for altering body mass composition in a human subject, themethod comprising: connecting the subject with a device which producesan electrical current by disposing electrodes at the subject's scalp ata location corresponding to each of the subject's left and rightvestibular systems; and applying galvanic vestibular stimulation (GVS)from the device to the subject via the electrodes to altering body masscomposition.
 2. The method of claim 1, wherein altering body masscomposition comprises decreasing total body fat, increasing relativepercentage lean muscle mass, and increasing bone mineral density in thehuman subject.
 3. The method of claim 2, wherein altering body masscomposition treats at least one of: diabetes, type 2 diabetes mellitus,hypertension, obesity, osteoporosis or an obesity-related disease. 4.The method of claim 1, further comprising treating the at least onedisease by applying GVS to the subject using a sinusoidal atapproximately 0.5 Hz with an approximately 50 percent duty cycle.
 5. Themethod of claim 1, further comprising treating the at least one diseaseby applying GVS for a predetermined period of time at regular intervals.6. A method for treating at least one disease in a human subject, themethod comprising: connecting the subject with a device which producesan electrical current by disposing electrodes at the subject's scalp ata location corresponding to each of the subject's left and rightvestibular systems; and treating the at least one disease by applyinggalvanic vestibular stimulation (GVS) from the device to the subject viathe electrodes, wherein the at least one disease is one or more ofdiabetes, type 2 diabetes mellitus, hypertension, obesity, osteoporosisor an obesity-related disease.
 7. The method of claim 6, whereinapplying GVS to the subject alters body mass composition.
 8. The methodof claim 7, wherein altering body mass composition comprises decreasingtotal body fat, increasing relative percentage lean muscle mass, andincreasing bone mineral density in the human subject.
 9. The method ofclaim 6, further comprising treating the at least one disease byapplying GVS to the subject using a sinusoidal wave at approximately 0.5Hz with an approximately 50 percent duty cycle.
 10. The method of claim6, further comprising treating the at least one disease by applying GVSfor a predetermined period of time at regular intervals.